CN103415617A - Apparatus and method for processing a sample - Google Patents
Apparatus and method for processing a sample Download PDFInfo
- Publication number
- CN103415617A CN103415617A CN2012800124145A CN201280012414A CN103415617A CN 103415617 A CN103415617 A CN 103415617A CN 2012800124145 A CN2012800124145 A CN 2012800124145A CN 201280012414 A CN201280012414 A CN 201280012414A CN 103415617 A CN103415617 A CN 103415617A
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- sample
- analyte capture
- capture element
- receiving element
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- B01L2300/069—Absorbents; Gels to retain a fluid
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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- B01L2400/00—Moving or stopping fluids
- B01L2400/04—Moving fluids with specific forces or mechanical means
- B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
- B01L2400/0487—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics
- B01L2400/049—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure fluid pressure, pneumatics vacuum
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Abstract
A first apparatus (100) for processing a liquid sample is disclosed. The apparatus (100) includes a sample-receiving (120), a filtrate-receiving component (150), and an analyte-capture element (170). The apparatus (100) forms a liquid flow path through which the sample passes, thereby causing the analyte-capture element (170) to capture an analyte, if present. A method is disclosed whereby a liquid sample is passed through the first (100) apparatus and the analyte-capture element (170) is easily separated from the apparatus for further processing and detection of the analyte. A structurally-related second apparatus (200) for processing a plurality of liquid samples, and a corresponding method of use, also is disclosed.
Description
The cross reference of related application
Present patent application requires to be filed in the U.S. Provisional Patent Application No.61/451 on March 9th, 2011,096 rights and interests, and this patent application is incorporated herein by reference in full.
Background technology
Polytype sample (for example clinical, environment, food and drink sample) is carried out to routine test to determine whether to exist microorganism.Specifically, several samples is tested to determine existing of pathogenic micro-organism.Usually, need to carry out polytype pre-treatment (that is, the processing before detecting step) in order to improve the quantity of target microorganism, quantity, the microorganism of concentrating that reduces non-target microorganism to sample, and/or reduce potential interference amount of substance in sample.Pre-treatment step may be required great effort, and may need to spend some hours and day complete to some.Develop multiple material and equipment and completed the required number of steps of sample pretreatment and time in order to minimizing.
May be difficult to process simultaneously a plurality of samples, in default of the required simple equipment efficiently of this program.Still need to be for the preparation of one or more samples to carry out the simple method of microorganism detection.
Summary of the invention
The present invention generally relates to the detection of microorganism in sample.Specifically, the invention provides first device and corresponding using method, whether described apparatus and method exist to detect the analyte relevant to microorganism for the treatment of sample.Advantageously, first device is constructed such that amount that it can reduce interfering substance in sample and with the easy steps analyte that just can concentrate.Then in another easy steps, the analyte concentrated can be transferred in container for subsequent disposal.The invention provides the second device and corresponding using method, whether described apparatus and method exist to detect the analyte relevant to microorganism in two or more samples for the treatment of a plurality of samples.Except having the advantage that first device provides, the second device also allows a plurality of analytes that concentrate are transferred to container simultaneously for subsequent disposal.
In one aspect, the invention provides the device for the treatment of sample.This device can comprise sample receiving element, filtrate receiving element and analyte capture element.The sample receiving element can comprise the first hollow body, and this first hollow body has the first end, the second end and from the first end, extends to the first Room of the second end; And filtering element, this filtering element is arranged in the first Room between the first end and the second end.The first end can comprise the first opening that is configured to hold sample, and the second end can comprise the second opening.The filtrate receiving element can comprise the second hollow body, and this second hollow body has the 3rd end, the 4th end and from the 3rd end, extends to the second Room of the 4th end.The 3rd end can comprise and is configured to hold the 3rd opening that sample holds the second end of member, and the 4th end can comprise the 4th opening.The analyte capture element can removably be connected to the filtrate receiving element.When the sample receiving element was connected to the filtrate receiving element, this device can be formed with and be beneficial to flow and cross the ，Gai fluid channel, fluid channel of the first Room, filtering element and the second Room and be conducive to the contact between fluid sample and analyte capture element.The second end can be formed and be proportional at least a portion that is fitted in the second Room is interior and vertically move at least a portion of passing the second Room.
In any of above-described embodiment, the analyte capture element also can be arranged in the second Room.
In any of above-described embodiment, this device also can comprise the detachable inner sleeve with the 5th end and the 6th end, and the 5th end has the 5th opening, and the 6th end has the 6th opening, and wherein said sleeve pipe is arranged in the second Room.In any of above-described embodiment, this device also can comprise porous supporting mass or foraminous shield.In any of above-described embodiment, at least a portion of porous supporting mass or foraminous shield can be arranged in the second hollow body between analyte capture element and the 4th opening.
In any of above-described embodiment, filtering element also can comprise a plurality of layers.
In any of above-described embodiment, the second end can be suitable for being inserted in the second Room and move through the point that the second Room arrives its contact analysis thing capture element, porous supporting mass or foraminous shield.
On the other hand, the invention provides a kind of device for the treatment of a plurality of samples.This device can comprise sample receiving element, filtrate receiving element and a plurality of analyte capture element.The sample receiving element can comprise the first main body, and this first main body has the first Room separated on the first end, the second end and a plurality of space, and each first Room extends to the second end from the first end; With a plurality of filtering elements, each filtering element is arranged in these a plurality of first Room, between the first and second openings.The first end can comprise a plurality of the first openings, and at least one first opening is configured to hold sample.The second end can comprise a plurality of outlets, and each outlet has the second opening.The first main body can form a plurality of fluid channels, and each passage extends to the second opening and passes the first Room therebetween from the first opening.The filtrate receiving element can comprise the second main body, and this second main body has the second Room separated on the 3rd end, the 4th end and a plurality of space, and each second Room extends to the 4th end from the 3rd end.Each second Room can comprise the 3rd opening that is positioned at the 3rd end, and the 3rd opening is configured to hold in these a plurality of outlets; With the 4th opening that is positioned at the 4th end.Each be connected to filtrate receiving element in these a plurality of analyte capture element.When the sample receiving element was connected to the filtrate receiving element, device can form a plurality of fluid channels; Each fluid channel is conducive to make flow to cross in in these a plurality of first Room, these a plurality of filtering elements and these a plurality of second Room, and is conducive to make these a plurality of analyte capture element of fluid contact at least one.Each in these a plurality of outlets can be formed and be proportional at least a portion that is fitted in the second Room is interior and vertically move at least a portion of passing the second Room.In any embodiment, at least one of this a plurality of analyte capture element also can be arranged at least one of these a plurality of the second Room.In any embodiment, this device also can comprise at least one the detachable inner sleeve with the 5th end and the 6th end, the 5th end has the 5th opening, and the 6th end has the 6th opening, and wherein said sleeve pipe is arranged at least one of these a plurality of the second Room.In any embodiment, this device also can comprise porous supporting mass or foraminous shield.In any embodiment, at least a portion of at least one porous supporting mass can be arranged at least one second Room between analyte capture element and the 4th end.In any embodiment, the analyte capture element can be connected to the porous supporting mass.In any embodiment, at least one filtering element also can comprise a plurality of layers.In any embodiment, each in these a plurality of outlets can be suitable for being inserted in these a plurality of second Room and move through the point that the second Room arrives its contact analysis thing capture element, porous supporting mass or foraminous shield.
In any of above-described embodiment, the 4th end can be configured to be connected to negative pressure source.In any of above-described embodiment, sample receiving element or filtrate receiving element also can comprise setting element, when the sample receiving element was connected to the filtrate receiving element, this setting element controllably kept the position of sample receiving element with respect to the filtrate receiving element.
Aspect another, the invention provides a kind of method that in sample, whether analyte exists that detects.The method can comprise provides liquid sample and for the treatment of the device of sample.This device can comprise sample receiving element, filtrate receiving element and analyte capture element.The sample receiving element can comprise the first hollow body, and this first hollow body has the first end, the second end and from the first end, extends to the first Room of the second end; And filtering element, this filtering element is arranged in the first Room between the first end and the second end.The first end can comprise the first opening that is configured to hold sample, and the second end can comprise the second opening.The filtrate receiving element can comprise the second hollow body, and this second hollow body has the 3rd end, the 4th end and from the 3rd end, extends to the second Room of the 4th end.The 3rd end can comprise and is configured to hold the 3rd opening that sample holds the second end of member, and the 4th end can comprise the 4th opening.The analyte capture element can removably be connected to the filtrate receiving element.When the sample receiving element was connected to the filtrate receiving element, this device can be formed with and be beneficial to flow and cross the ，Gai fluid channel, fluid channel of the first Room, filtering element and the second Room and be conducive to the contact between fluid sample and analyte capture element.The second end can be suitable for being inserted in the second Room and move through the part of the second hollow body.The method also can comprise makes that liquid sample flows through filtering element, the liquid after making to filter with the contact of analyte capture element, the analyte capture element is separated with device, and detect whether there is analyte.
In any of above-described embodiment, the method also can comprise device is attached to negative pressure source, wherein make liquid sample flow through filtering element further comprise with negative pressure pull sample make its pass filtering element with generate filter after sample.In any of above-described embodiment of the method, by negative pressure, pull sample to make it pass filtering element and also can comprise that by negative pressure, making to filter rear sample contacts with the analyte capture element.In any of above-described embodiment of the method, the analyte capture element is separated with device also can comprise with the second end the analyte capture element is separated with device.In any of above-described embodiment of the method, use the second end also can comprise to promote the second end and pass the second Room with the separate analytes capture element.In any of above-described embodiment, after the method also can be included in the separate analytes capture element, by lysis agent Treatment Analysis thing capture element.
Aspect another, the invention provides a kind of method that whether has analyte in a plurality of samples that detects.The method can comprise provides plurality of liquid sample and device.This device can comprise sample receiving element, filtrate receiving element and a plurality of analyte capture element.The sample receiving element can comprise the first main body, and this first main body has the first Room separated on the first end, the second end and a plurality of space, and each first Room extends to the second end from the first end; With a plurality of filtering elements, each filtering element is arranged in these a plurality of first Room, between the first and second openings.The first end can comprise a plurality of the first openings, and at least one first opening is configured to hold sample.The second end can comprise a plurality of outlets, and each outlet has the second opening.Each in these a plurality of first Room can form from one these a plurality of the first openings to the fluid channel of in these a plurality of second openings.The filtrate receiving element can comprise the second main body, and this second main body has the second Room separated on the 3rd end, the 4th end and a plurality of space, and each second Room extends to the 4th end from the 3rd end.Each second Room can comprise the 3rd opening that is positioned at the 3rd end, and the 3rd opening is configured to hold in these a plurality of outlets; With the 4th opening that is positioned at the 4th end.Each be connected to filtrate receiving element in these a plurality of analyte capture element.When the sample receiving element was connected to the filtrate receiving element, device can form a plurality of fluid channels; Each fluid channel is conducive to make flow to cross in in these a plurality of first Room, these a plurality of filtering elements and these a plurality of second Room, and is conducive to make at least one in these a plurality of analyte capture element of fluid contact.In these a plurality of outlets, each can be suitable for being inserted in these a plurality of second Room and move through the part of the second Room.The method also can comprise makes at least two kinds of liquid samples flow through at least two in these a plurality of filtering elements, with liquid after generating liquid after at least two kinds of filtrations, making these at least two kinds of filtrations, with at least two analyte capture element, contact, make these at least two analyte capture element to separate with device, and whether detection exist analyte.In any embodiment, the method also can comprise device is attached to negative pressure source, wherein makes this plurality of liquid sample flow cross these at least two filtering elements and further comprises by negative pressure and pull liquid sample to make it pass these at least two filtering elements to produce sample after at least two kinds of filtrations.In any of the embodiment of the method, by negative pressure, pull these a plurality of samples to make it pass these at least two filtering elements and also can comprise that by negative pressure, making to filter at least two analyte capture element of rear sample and this contacts.In any embodiment, these at least two analyte capture element are separated with device also can comprise with at least two outlets these at least two analyte capture element are separated with device.In any embodiment, use at least two outlets also can comprise that these at least two second Room are passed at least two outlets of promotion this this so that these at least two analyte capture element are separated with device.In any of above-described embodiment, after the method also can be included at least two analyte capture element of separation, process this at least two analyte capture element with the lysis agent.
Word " preferably " and " preferably " refer to may provide in some cases the embodiment of the present invention of some beneficial effect.Yet in identical situation or other situations, other embodiment may be also preferred.In addition, the statement of one or more preferred embodiments is not implied to other embodiment are not available, and be not intended to other embodiment are got rid of from scope of the present invention.
When term " comprises " and its modification while occurring in specification sheets and claims, these terms do not have restrictive sense really.
" a kind of (individual) " used herein, " described (being somebody's turn to do) ", " at least a (individual) " and " one or more (one or more) " are used interchangeably.Therefore, for example, microorganism can be interpreted as meaning " one or more " microorganism.
Term " and/or " mean one of listed key element or all, or the combination of any two or more key elements of listed key element.
In addition, the numerical range explained by end points of this paper comprises in described scope all numerical value of comprising (for example, 1 to 5 comprise 1,1.5,2,2.75,3,3.80,4,5 etc.).
Foregoing invention content of the present invention is not intended to describe each disclosed embodiment of the present invention or every kind of embodiment.Below describe more specifically exemplified with exemplary embodiment.In the application some places in full, by example list, provide guidance, these examples can be used in various combinations.Under each situation, cited list is as just representative group, and should not be understood to the exclusiveness list.
Below in conjunction with accompanying drawing and description, introduce the more details of above-mentioned and other embodiment.By description, accompanying drawing and claims, can fully understand other features, target and advantage.
The accompanying drawing explanation
Fig. 1 is the partial, exploded perspective view for an embodiment according to a kind of device for the treatment of sample of the present invention.
Fig. 2 A is the broken section skeleton view of the apparatus for assembling of Fig. 1, this apparatus for assembling operationally be connected to the container be connected with negative pressure source.
Fig. 2 B be in the first operation configuration Fig. 2 A device and with the partial, exploded perspective view of the container of its use.
Fig. 2 C is in the apparatus for assembling of Fig. 2 B of the second operation configuration and the broken section skeleton view of container.
Fig. 3 is the cross-sectional side view of the sample receiving element of Fig. 1 device.
Fig. 4 is the side-view according to an embodiment of filtering element of the present invention.
Fig. 5 A is the cross-sectional side view of the filtrate receiving element of Fig. 1 device.
Fig. 5 B is the partial side view of an embodiment of the filtrate receiving element that is connected with the analyte capture element on it.
Fig. 6 A is the decomposition side view that is arranged on an embodiment of the analyte capture element between porous supporting mass and foraminous shield.
Fig. 6 B is the decomposition side view that is arranged on another embodiment of the analyte capture element between porous supporting mass and foraminous shield.
Fig. 7 A is the cross-sectional side view of Fig. 2 B device.
Fig. 7 B is in the apparatus for assembling of Fig. 7 A of the first operation configuration and the cross-sectional side view of container.
Fig. 7 C is the cross-sectional side view of apparatus for assembling that is in Fig. 7 B of the second operation configuration, and wherein container operationally is attached on described device.
Fig. 8 is the decomposition diagram according to an embodiment of a kind of device for the treatment of a plurality of samples of the present invention.
Fig. 9 is the cross-sectional side view of device that is in Fig. 8 of the first operation configuration.
Figure 10 is the bottom perspective view of the filtrate receiving element of Fig. 9 device.
Embodiment
The present invention relates generally to and prepares sample and whether have analyte to detect.Specifically, the invention provides a kind of like this apparatus and method, described apparatus and method are conducive to from liquid sample, removing relatively large particulate matter, and are conducive to trap analyte for subsequent analysis.Advantageously, can only by a step or two steps, complete the analyte trapping with described device.The analyte that gained traps relatively concentrates, relatively free from foreign meter, and be applicable to multiple detection method (for example immunologic detection method and nucleic acid detection method).
The present invention includes the method and apparatus for the treatment of single sample.The present invention also comprises for processing simultaneously the method and apparatus of a plurality of samples.The inventive method relates to the detection to analyte in sample.In any embodiment, described analyte can be biological analyte, for example shows in sample the biological analyte that has microorganism.
Sample can be any sample that possible comprise biological analyte.The non-limitative example of appropriate samples comprises suspension or culture, environmental sample (as surperficial swab), food (as the sample in starting material, the course of processing and finished product sample), beverage, clinical sample (as blood, urine, sputum, tissue, mucus, ight soil, Wound exudate, fester) and the water (as surface water, tap water, process water) of cell (as mammalian cell, insect cell, yeast cell, filamentous fungus, bacterial cell).
The non-limitative example of suitable biological analyte comprises nucleic acid (for example, the polynucleotide relevant to specific cell type or microorganism) but or detectable antigens (for example, protein, oligopeptides, enzyme, intracellular toxin, cell membrane component, and cell wall constituent).The routine analyzer of detection of biological analyte is well known in the art.The preferred biological analyte detected for example comprise can reaction (for example, PCR) in the nucleic acid of amplification.
Except fluid sample, other specimen also may comprise liquid and are dissolved in or are suspended in one or more solids in liquid medium.The sample of paying close attention to can comprise process flow, water, soil, plant or other vegetation, air, surface (such as the surface of polluting) etc.Sample can also comprise cultured cells.Sample can also be included on device (as, biological indicator device) or among sample, comprise cell, spore or enzyme.
Solid sample can (as, by mixing, ultrasonic degradation, homogenizing) cracked, and can be suspended in liquid (as, water, damping fluid, meat soup) in.In certain embodiments, can use in the method the sample collecting apparatus that contains specimen material (as, swab, sponge).Perhaps, can from the sample collecting apparatus elution (as, flush out, scrape, squeeze out) specimen material, then in described method, use specimen material.In certain embodiments, the liquid or solid sample can liquid (as, water, damping fluid, meat soup) in the dilution.
Appropriate samples also comprises cell suspension liquid medium (as culture broth, semi-solid cell culture medium and tissue culture medium (TCM), filtrate), the cell that this cell suspension liquid medium comprises cell or comprises before this.Appropriate samples also comprises cell pyrolysis liquid.Can prepare cell pyrolysis liquid by chemical mode (as washing composition, enzyme), mechanical system (sound vibration, homogenize, French press) or other lysis modes known in the art.
Microorganism (for example, bacterium, fungi, virus) is the source that can detect analyte.Can be able in the specimen from multiple source as described herein, analyze microorganism.The microorganism merited attention especially comprises protokaryon and eukaryote, especially gram positive bacterium, gram negative bacterium, fungi, protozoon, mycoplasma, yeast, virus and the even virus that coats of lipid.Relevant biology comprises enterobacteriaceae (Enterobacteriaceae) or micrococcaceae (Micrococcaceae) or Staphylococcus (Staphylococcus spp.) especially, streptococcus (Streptococcus spp.), Rhodopseudomonas (Pseudomonas spp.), enterococcus spp (Enterococcus spp.), salmonella (Salmonella spp.), legionella (Legionella spp.), Shigella (Shigella spp.) yersinia's genus (Yersinia spp.), enterobacter (Enterobacter spp.), Escherichia (Escherichia spp.), bacillus (Bacillus spp.), Listeria (Listeria spp.), Vibrio (Vibrio spp.), corynebacterium (Corynebacteria spp.) and simplexvirus, Aspergillus (Aspergillus spp.), the member of Fusarium (Fusarium spp.) and mycocandida (Candida spp.).The biology that virulence is strong especially comprises streptococcus aureus (Staphylococcus aureus) (comprising endurance strain such as methicillin-resistant staphylococcus aureus (MRSA)), staphylococcus epidermidis (S.epidermidis), streptococcus pneumoniae (Streptococcus pneumoniae), streptococcus agalactiae (S.agalactiae), micrococcus scarlatinae (S.pyogenes), enterococcus faecalis (Enterococcus faecalis), vancomycin-resistant enterococcus (Vancomycin Resistant Enterococcus(VRE)), vancomycin resistance streptococcus aureus (Vancomycin Resistant Staphylococcus aureus(VRSA)), the streptococcus aureus of medium tolerance vancomycin (Vancomycin Intermediate-resistant Staphylococcus aureus(VISA)), Bacillus anthracis (Bacillus anthracis), Pseudomonas aeruginosa (Pseudomonas aeruginosa), intestinal bacteria (Escherichia coli), aspergillus niger (Aspergillus niger), Aspergillus fumigatus (A.fumigatus), rod aspergillus (A.clavatus), Fusarinm solani (Fusarium solani), Fusarium oxysporum (F.oxysporum), fusarium chlamydosporum (F.chlamydosporum), listeria monocytogenes (Listeria monocytogenes), Yi Shi listeria spp (Listeria ivanovii), vibrio cholerae (Vibrio cholera), Vibrio parahemolyticus (V.parahemolyticus), hog cholera Sharpe bacillus (Salmonella cholerasuis), typhoid fever Sharpe bacillus (S.typhi), Salmonella typhimurium (S.typhimurium), Candida albicans (Candida albicans), Candida glabrata (C.glabrata), monilia krusei (C.krusei), Enterobacter sakazakii (Enterobacter sakazakii), Escherichia coli O 157 and multidrug resistance gram negative bacillus (MDR).
Gram positive bacterium and gram negative bacterium merit attention especially.Even more it is worth noting gram positive bacterium, for example streptococcus aureus.And, special concern be the antibiotic resistance microorganism that comprises MRSA, VRSA, VISA, VRE and MDR.
Fig. 1 shows the decomposition perspective upper view according to an embodiment of first device 100 of the present invention.First device 100 comprises sample receiving element 120 and filtrate receiving element 150.Sample receiving element 120 comprises the first hollow body 121, and this first hollow body has the first end 124 and second end 126 relative with the first end 124.The first end comprises the first opening 132.The first opening is configured to hold sample.For example, the size of the first opening 132 can be configured to receive liquid transfer gun head, and liquid sample can be transferred in the first hollow body 121 by liquid transfer gun head.
Fig. 2 A shows the side elevation in partial section of assembling first device 100 of Fig. 1, and this has been assembled first device and operationally has been connected to waste container 300.First device 100 is shown as and is in the first operation configuration, as will be hereinafter in detail as shown in and described like that.In this configuration, the second end (not shown) of sample receiving element 120 is inserted in filtrate receiving element 150, and first device 100 is ready to sample is received in the first opening 132.Can find out, in this configuration, setting element 180 contact adjusting sheets 157, thus for sample receiving element 120, towards the movement of filtrate receiving element 150, provide appropriate resistance (resistance that for example, can be overcome by appropriate manual force) with direction shown in arrow " A ".Setting element 180 prevents that the first hollow body 121 from moving further in the second hollow body 151, until sample receiving element 120 and filtrate receiving element 150 are outwards departed from collar 155(namely by enough moving setting elements 180 that makes of trying hard to recommend together, approximately perpendicular to arrow " A "), thus allow the second end 126 of the first hollow body 121 to move further into filtrate receiving element 150.
Fig. 2 B shows the partial, exploded perspective view that Fig. 2 A has assembled first device 100, wherein container 400(for example, test tube, micro test tube etc.) be attached to the 4th end 156 of filtrate receiving element 150.When assembling fully, container 400 for example, arrives the 4th opening (not shown, referring to Figure 10) of filtrate receiving element 150 in separable mode attached (, frictional fit), and is provided so that four opening of vessel port towards filtrate receiving element 150.
Fig. 2 C shows the skeleton view of assembling first device 100 of Fig. 2 B that is in the second operation configuration.Container 400 inserts the 4th opening 164 of filtrate receiving element 150.Can find out, in this operation configuration, the second end 126 of sample receiving element 120 inserts the filtrate receiving element fully.
Fig. 3 shows the cross-sectional side view of Fig. 1 sample receiving element 120.Sample receiving element 120 comprises the first hollow body 121, and this first hollow body has the first Room 130 that extends to the second end 126 from the first end 124.The first end 124 comprises the first opening 132.The second end 126 comprises the second opening 134.The first Room 130 is cylindrical in the illustrated embodiment, but other shapes may be also suitable.Can find out, the part of first Room 130 contiguous the first ends 124 has the diameter of the part that is greater than contiguous the second end 126 in the first Room.Although this feature is not essential, it may be desirable in certain embodiments.The liquid fluid passage that the first Room 130 forms from the first opening 132 to second openings 134.The second opening 134 is less than the first opening 132.Due to the second opening 134, be less than the internal diameter of the first hollow body 121, so platform 135 forms at the second end 126 places of the first hollow body 121.Platform 135 is formed for the supporting mass of filtering element 140.Although illustrated embodiment shows platform 135, be positioned at contiguous the second end 126 places, also it is contemplated that out, in certain embodiments, platform 135 can be positioned at the position of the first end 124 of more close hollow body 121.Setting element 180 as herein described also is shown in Fig. 3.
The first hollow body 121 can pass through injection molding, for example for example, by polymer materials (, polyethylene, polypropylene, polystyrene, polycarbonate), is made.Alternatively, the first hollow body 121 can be used glass or metal to make.
Fig. 4 shows an embodiment of the filtering element 140 that comprises a plurality of layers.Lines A shows the direction that flow is crossed filtering element 140.Layer 142 is the first layer of sample from the multi-layer filter element 140 that wherein flows through.The relatively coarse non-woven deep filter (approximately 1mm is thick) that layer 142 can comprise film filter or be made by polyethylene fibre.Layer 142 can have the nominal porosity of about 20-50 μ m, and can be used for preventing that macrobead from flowing into other layers of filtering element 140.Layer 143 can comprise wet paving fibrous framework (approximately 0.2-1mm is thick), for example comprises alternatively, from liquid sample, removing the particulate matter of one or more specific non-analyte substances (, fat, mineral substance).For example, although layer 143 can have the further nominal porosity (, 10-20 μ m) from removing particulate matter sample, fiber and/or particulate matter also can be optionally from liquid sample, removing fatty ingredient, and basically not from liquid, removing bacterium.Layer 144 comprises filtering material, and it for example, for almost completely removing the particulate matter that is greater than bacterium (, >=5 μ m diameter).Separately mode or with the arbitrary combination mode of other materials for the non-limitative example of the material of filtering element 140, be that (Part No. is NB005PPS2R to the polypropylene mat filter, the nominal porosity is 5 μ m, can derive from the female promise of 3M (the CUNO 3M of company on sale in the plum of the Connecticut State, Meriden, CT)).Can in filtering element 140, use other known layer (not shown) and/or materials, wherein the effect of each layer is when liquid sample flows through filtering element 140, reduces the non-analyte amount of substance in it.
Fig. 5 A shows the cross-sectional side view of the filtrate receiving element 150 of Fig. 1.Filtrate receiving element 150 comprises the second hollow body 151, and this second hollow body has setting lining 158 in the inner.The second hollow body 151 that is provided with optional lining 158 in it forms the second Room 160 that extends to the 4th end 156 from the 3rd end 154.The 3rd end comprises the 3rd opening 162.The 4th end 156 comprises the 4th opening 164.Thereby the second Room 160 forms the liquid fluid passage that extends to the 4th opening 164 of the second hollow body 151 from the 3rd opening 162.The second hollow body 151 also comprises the collar 155 that is positioned at the 3rd end 154 places.During use, collar 155 can be connected to the container (as shown in Figure 2) be operably connected with negative pressure source, makes it pass first device 100 to be conducive to moving liquid.
The second hollow body 151 can pass through injection molding, for example for example, by polymer materials (, polyethylene, polypropylene, polystyrene, polycarbonate), is made.Alternatively, the second hollow body 151 can be used glass or metal to make.
Porous supporting mass 172 and foraminous shield 176 all can be made by multiple porous material, (for example for example allow liquid, liquid, aqueous) from the cellulosic fibre that wherein flows through, synthon (for example, polymkeric substance, glass), foam (for example, open celled foam, such as urethane), for example, with sintered glass material (, glass, pottery, polymkeric substance).Preferably, when foraminous shield 176 existed, it comprised the nominal porosity and is greater than approximately 5 μ m, is preferably more than the approximately material of 10 μ m, made microorganism can pass freely through material and arrived analyte capture element 170.The non-limitative example that can be used for the material of foraminous shield 176 is polypropylene mat filter (Part No. is NB005PPS2R, and the nominal porosity is 5 μ m, can derive from the female promise of 3M company (CUNO 3M, Meriden, CT) on sale in the plum of the Connecticut State).
The size of porous supporting mass 172, analyte capture element 170 and foraminous shield 176 is designed so that it can insert slidably (for example,, by pressing) and releaseably remain in lining 158 or the second hollow body 151.(not shown) in certain embodiments, analyte capture element 170 (for example can connect, with adhesive method connection, stitching, heat bonding) to porous supporting mass 172 and/or foraminous shield 176, precondition is that described connecting mode basically can not prevent the contact between liquid sample and analyte capture element 170 and/or can not prevent that basically liquid sample from flowing through analyte capture element 170.
Analyte capture element 170 comprises the material that is configured to trap and keep target analytes.In certain embodiments, analyte capture element 170 comprises porous filter, this porous filter allow liquid by but retain the particle that is approximately bacterium size (approximately 0.5 to approximately 5 μ m).Analyte capture element 170 for example can for example, in multiple film formula strainer (, cellulose acetate filter, nylon filter, nitrocellulose filters, polycarbonate filter, porcelain filter) one or more.The non-limitative example of suitable membrane formula strainer is VERSAPOR 3000TN film (3 μ m nominal porosity) and VERSAPOR800 film (0.8 μ m nominal porosity), both all can derive from quite that (the Pall Life Sciences of life science company at port, Washington, New York, Port Washington, NY).Optionally, filtering material can comprise coupling binding partners (for example, polyclonal antibody, monoclonal antibody, acceptor, lectin) thereon.In certain embodiments, binding partners can be provided for the specificity in conjunction with particular target analytes.Fig. 6 A shows the exploded view of a configuration of the analyte capture element 170 that comprises porous filter.Analyte capture element 170(is 0.45 μ m film filter for example) be sandwiched between porous supporting mass 172 and foraminous shield 176.Porous supporting mass 172 and foraminous shield 176 all can for example form in the following manner: use punch die foam materials (for example, polyurethane foam) to be cut into to the diameter had allowing it with the wall formation frictional fit of the second Room 160.
Alternatively or in addition, analyte capture element 170 ' can comprise particulate matter (for example, fiber, particle, pearl) or the atresia flaky material (for example, polymeric film) that is configured to be attached to target analytes.In certain embodiments, particulate matter can be porous.In certain embodiments, particulate matter can be atresia.In certain embodiments, analyte capture element 170 can comprise the combination of porous and non-porous particle material.
In certain embodiments, particulate matter combining target analyte relatively non-specifically.The agent of concentrating of some granular cell is as known in the art and is applicable to method of the present invention.The concentrate non-limitative example of agent of suitable cell comprises gac, hydroxyapatite (Berry et al.; Appl.Environ.Microbiol.;
63: the people such as 4069-40741997(Berry, " application and environmental microorganism ", the 63rd volume, 4069-4074 page, 1997)), magnetic bead (Oster et al., J.Magnetism and Magnetic Mat.;
225: 145-150; The people such as 2001(Oster, " magnetics and magneticsubstance magazine ", the 225th volume, 145-150 page, calendar year 2001), ferrimagnetism mineral, magnetite, chitosan and affiliation carrier.With the composition that comprises the immobilization metal solid support material, describe to some extent in the open No.WO2008/134472 of PCT patent from trapping sample or the microorganism of concentrating, this patent openly is incorporated herein by reference in full.
Exemplary particulate matter also comprises diatomite and surface-treated diatomite.The object lesson of this agent of concentrating is found in the U.S. Patent Application Publication No.2010/0209961 of common transfer, and the disclosure of this patent application is incorporated herein by reference.When being scattered in or be suspended in aqueous systems, inorganic materials presents material and the distinctive surface charge of aqueous systems pH.Current potential across material-water termination is called " zeta-potential ", and it can be calculated by electrophoretic mobility (that is the speed, moved between the charging electrode of material particle in being arranged at aqueous systems).In one embodiment, the ζ-potential that can have at least more on the occasion of some is compared in the agent of concentrating with undressed diatomite, and the agent of concentrating can be surprisingly than can significantly more effectively concentrate microorganism (its surface is usually often electronegative) such as bacterium of undressed diatomite.
In certain embodiments, particulate matter can comprise coupling binding partners thereon, and binding partners can be provided for the specificity in conjunction with particular target analytes.In certain embodiments, particulate matter can be incorporated into to matrix (for example, being embedded in the pearl in fibrous matrix).Fig. 6 B shows the exploded view of a configuration of the analyte capture element 170 ' that comprises particulate matter (for example, hydroapatite particles).Analyte capture element 170 ' is sandwiched between porous supporting mass 172 and foraminous shield 176.Porous supporting mass 172 and foraminous shield 176 all can such formation as described herein.
Fig. 5 B shows the schematic side elevation according to the part of the 4th end 156 of filtrate receiving element 150 ' of the present invention.In Fig. 5 A, the analyte capture element 170 be arranged in lining 158 is sandwiched between porous supporting mass 172 and foraminous shield 176, lining 158 is arranged in the second Room 160, by contrast, the analyte capture element 170(of the present embodiment is film filter for example) releaseably at the second end 156 places, for example be connected to the second hollow body 152(, by binder layer, not shown).(for example can adopt other connecting modes, ultra-sonic welded, heat bonding), precondition is that described connecting mode basically can not prevent the contact between liquid sample and analyte capture element 170 and/or can not prevent that basically liquid sample from flowing through analyte capture element 170.
Fig. 7 A shows the cross-sectional side view of the first device 100 of Fig. 2 B that is in the first operation configuration.The second end 126 of the first hollow body 121 is formed and is proportional at least a portion that is fitted in the second Room 160 is interior and vertically move at least a portion of passing this second Room.In the first operation configuration, the second end 126 of the first hollow body 121 inserts in lining 158, this lining is arranged in the second Room 160 of the second hollow body 151, outside surface with the second end 126 by making the first hollow body 121 overlays on lining 158, then overlays and on the internal surface of the second hollow body 150, reaches the formation degree of anti-leak of liquid sealing basically.In the illustrated embodiment, should be noted that, the second end 126 of the first hollow body 121 enough inserts in the second hollow body 151 the second opening 134 is positioned to contiguous foraminous shield 176 deeply.When first device 100 was set to be in the first operation configuration, the second end 126 should enough insert in the second hollow body 151 deeply and seal to form, but will not be positioned to be close to foraminous shield 176 by the second opening 134.
While being in the first work point, first device 100 is ready to hold and processing sample.Thereby, while being in the first work point, formation extends through the first Room 130, filtering element 140, the second opening 134, the second Room (not shown), the 4th opening 164 from the first opening 132, and arrives or pass the liquid fluid passage of analyte capture element 170.Can sample receiving element 120 and filtrate receiving element be set to the first work point before or after, filtrate receiving element 150 is connected to (for example, by collar 155) to waste container 300, as shown in Figure 2.Then can liquid sample be transferred in the first Room 130 by the first opening 132, and can be by waste container 300 being applied to negative pressure (if existence) or by run by gravity, sample being pulled and passes the liquid fluid passage.
When liquid sample is transferred in the first Room 130, can carry out supporting device by waste container 300, as shown in Figure 2 A.The liquid sample (not shown) is shifted to (for example, by toppling over or moving liquid) to the first Room 130, and allow it to flow through filtering element 140 to enter the second Room 160 and with analyte capture element 170, contact and/or flow through this analyte capture element.In certain embodiments, liquid sample can flow through device by run by gravity.In certain embodiments, can promote liquid and flow through first device 100(as shown in Figure 2 by the 4th opening 164 being applied to negative pressure).Can flow through first device 100 by making continuously minute style liquid samples such as two parts of comparatively large vol or many parts flow through the liquid sample that first device 100 makes large volume.In certain embodiments, the volume of the first Room 130 is at least about one milliliter.In certain embodiments, the volume of the first Room 130 is at least about five milliliters.In certain embodiments, the volume of the first Room 130 is at least about ten milliliters.In certain embodiments, the volume of the first Room 130 is at least about 25 milliliters.In certain embodiments, the volume of the first Room 130 is at least about 100 milliliters.
After liquid sample flow through first device 100, analyte capture element 170 was separated with first device 100.At first, first device 100 separates with waste container 300, if described waste container is for pulling liquid sample to pass first device 100.The 4th end 156 of first device 100 is arranged on the top of container (for example, test tube, not shown) opening, or optionally, container is attached in separable mode the 4th opening 164 that first device 100 makes the vessel port facing device, as shown in Fig. 2 B.Sample receiving element 120, filtrate receiving element 150 or the two are applied to power, make and push it to together.This power should be enough to make setting element 180 as described above to extrinsic deflection, thereby allows the second end 126 of sample receiving element 120 further to pass the second Room 160 of filtrate receiving element 150, thereby first device 100 is arranged to be in the second operation configuration.
Fig. 7 B shows the exploded viewgraph of cross-section of assembling first device 100 and container 400 of Fig. 2 B.Should be noted that, when first device 100 was in this first operation configuration, lining 158 was arranged in the second Room (not shown) of filtrate receiving element 150, and the second end 126 of sample receiving element 120 inserts in lining 158 slidably.Should be noted also that in this configuration, the second end of sample receiving element 120 preferably should not pass the second Room 160 and reach the degree of mobile foraminous shield 176, analyte capture element 170 or porous supporting mass 172.
Fig. 7 C shows the cross-sectional side view of the first device 100 of Fig. 2 C that is in the second operation configuration.In this configuration, towards filtrate receiving element 150, promote sample receiving element 120, until the second position that setting element 180 arrives with respect to filtrate receiving element 150.In this position, the second end 126 of sample receiving element 120 enough moves in the second hollow body 151 with mobile foraminous shield 176, analyte capture element 170 and porous supporting mass 172 deeply, thereby make foraminous shield 176, analyte capture element 170 and porous supporting mass 172 with first device 100, separate (for example, releasing).If analyte capture element 170 both be not connected to foraminous shield 176 and has not been connected to porous supporting mass 172 yet, they can be spontaneously separated from one another.Advantageously, this can exposure analysis thing capture element for example, for subsequent disposal (, exposing cell cracking agent).In this operation configuration, analyte capture element 170 is pushed into easily in container 400 and is further processed like that with as described herein.
On the other hand, the invention provides the device for the treatment of a plurality of samples.Fig. 8 shows the decomposition perspective upper view according to an embodiment of the second device 200 of the present invention.Can find out, the second device 200 is similar to the first device 100 of Fig. 1-7 on structure and function, and different is that the second device 200 structurally is configured to process a plurality of samples.In certain embodiments, can in the second device 200, process simultaneously a plurality of samples.
The second device 200 comprises sample receiving element 220 and filtrate receiving element 250.Sample receiving element 220 comprises the first main body 221, and this first main body has the first end 224 and second end 226 relative with the first end 224.The first end comprises a plurality of the first openings 232.The first opening 232 is configured to hold sample.For example, the size of the first opening 232 can be configured to receive liquid transfer gun head, and liquid sample can be transferred in the first hollow body 221 by liquid transfer gun head.The second end comprises a plurality of outlets 233, and each outlet has the second opening 234.
Sample receiving element 220 also comprises optional setting element 280.Setting element 280 can play a role temporarily that sample receiving element 220 is remained on to basically fixing position with respect to filtrate receiving element 250, as shown in the first device 100 in Fig. 2 A-2C and described like that.Setting element 280 can with collaborative the playing a role of structure be present on filtrate receiving element 250, as shown in the first device 100 in Fig. 2 A-2C and described like that.
The first main body 221 and/or the second main body 251 can be passed through injection molding, for example for example, by polymer materials (, polyethylene, polypropylene, polystyrene, polycarbonate), are made.Alternatively, the first main body 221 and/or the second main body 251 can be used glass or metal to make.
Fig. 9 shows the cross-sectional side view of the second device 200 of Fig. 8.The second device 200 is in the first operation configuration (for example, setting element 280 contacts with trim plate 257), thereby it is ready to liquid sample is held and enters in this a plurality of the first Room 230 one or more.Illustrated embodiment shows and assembles a plurality of liquid fluid passages of the second device 200 formation, each fluid channel extends through the first Room 130, filtering element, the second Room (not shown) from the first opening 232, and is arranged on the analyte capture element 170 between foraminous shield 176 and porous supporting mass 172.
Figure 10 shows the bottom broken section skeleton view of the second end 256 of the filtrate receiving element 250 of Fig. 9 second device 200.The 4th end 256 comprises a plurality of the 4th openings 264, and described a plurality of the 4th openings are formed and are proportional for example, for holding the opening end of container (, pipe), as shown in the first device 100 in Fig. 2 B-2C and described such.A plurality of linings 258 also are shown in Figure 10, and each lining comprises the 6th opening 259.It in each lining 258 is porous supporting mass 272 that contiguous the 6th opening 259 is arranged on.
In an embodiment (not shown) of the first main body, the first Room is spaced apart with certain configuration, this configuration allows at least one other liquid fluid channel separation at least one liquid fluid passage (that is, comprising connection the first Room and outlet thereon) and these a plurality of liquid fluid passages.The separating liquid fluid channel causes forming the first hollow body substantially, as shown in Figure 3 with described.Optionally, each in the separable liquid fluid channel of this embodiment also can comprise setting element, as described herein.
Can in the method for processing sample, use any embodiment of first device 100 or the second device 200.The second device 200 can be used for sample of primary treatment, or it also can be used for processing simultaneously two or more samples.Can process to detect in each sample whether have an analyte (for example, microorganism) to sample.Advantageously, device of the present invention allows to remove pollution substance in sample the analyte in the sample that concentrates in an easy steps.The method comprises makes liquid sample flow through filtering element 140.In certain embodiments, can use negative pressure (for example, first device 100 being connected to negative pressure source 325, as described herein) to pull sample to make it pass filtering element 140 to produce filtrate.
The method also comprises makes filtrate contact analysis thing capture element 170 with the trapping analyte.In certain embodiments, can in a step, realize filtering and trapping.In certain embodiments, filtrate contact analysis thing capture element can being comprised for example makes filtrate flow cross porous analyte capture element (for example, film filter) by absorption or filtration, to trap analyte.In certain embodiments, filtrate contact analysis thing capture element can be comprised and (for example for example make filtrate and granular analyte capture element, hydroxyapatite, ion exchange resin, the coated particle of antibody) the fluid connection, by non-specific adsorption or by affine combination, to trap analyte.
The method also comprises makes analyte capture element 170 separate with first device 100.Advantageously, the design of first device 100 and the second device 200 provides a kind of simple mode, analyte capture element 170 can adopt a simple motion just with described device, to separate (for example, sample receiving element and filtrate receiving element are pushed to a part of contact analysis thing capture element of impelling together the sample receiving element and by it from the filtrate receiving element, releasing) by this mode.Advantageously, the design of first device 100 and the second device 200 allows container 400 before the separate analytes capture element, to be connected to described device alternatively.This allows the operator that the analyte capture element is directly pushed with the attached container of separable mode from first device 100, thereby has reduced to greatest extent the possibility that grasping and/or the analyte capture element of analyte capture element are polluted.In addition, attached container 400 also can comprise that reagent is to process the analyte by the analyte trap element traps.The operator can carry out selective reagents according to concrete analyte and detection method.
For example, in certain embodiments, analyte may be whole microorganism, for example bacterium.In certain embodiments, analyte may be living microorganism.In these embodiments, maybe advantageously by culture technique, detect microorganism.Therefore, can come from the analyte capture element, separating or the wash-out microorganism by the analyte capture element in rinsing and/or homogenizing suspension medium (water, damping fluid, buffer saline, liquid nutrient medium).Liquid suspension medium can be used for inoculation medium (for example, suitable nutrient agar) to determine in initial sample, whether target microorganism exists or measure its amount.In certain embodiments, analyte can be trapped to medium directly transfers on substratum to grow and to analyze.Therefore, when by the analyte capture element being pushed in container when the analyte capture element is separated with device, this container can comprise suspension medium within it.
In certain embodiments, analyte can be the part (for example, cell walls or its fragment, cytolemma or its fragment, protein or polysaccharide) of whole microorganism or microorganism.In these embodiments, maybe advantageously use immunologic diagnosis method (for example, ELISA, immunochromatographic method) to detect analyte.Therefore, when by the analyte capture element being pushed in container when the analyte capture element is separated with device, this container (for example can comprise suspension medium, lysis agent within it, acid, alkali, washing composition, enzyme, proteolytic enzyme, N,O-Diacetylmuramidase, lysostaphin), and/or analyte specific binding partner (for example, antibody, acceptor).
In certain embodiments, analyte can be and specified microorganisms or micropopulation involved enzyme or enzyme substrates (for example ATP).In these embodiments, maybe advantageously with enzyme assay, detect analyte.Therefore, when by the analyte capture element being pushed in container when the analyte capture element is separated with device, this container (for example can comprise suspension medium, lysis agent within it, acid, alkali, washing composition, enzyme, proteolytic enzyme, N,O-Diacetylmuramidase, lysostaphin), enzyme (for example, luciferase, Myokinase), and/or enzyme substrates (for example, fluorescein, colour developing enzyme substrates, or luciferase substrate).
In certain embodiments, analyte can be the polynucleotide (for example, DNA or RNA) that microorganism is relevant.In these embodiments, maybe advantageously use nucleic acid detection method as known in the art (for example, polymerase chain reaction method, RT-polymerase chain reaction method, ligase chain reaction method, nucleotide sequence dependent amplification method, engram analysis method) to detect analyte.Therefore, when by the analyte capture element being pushed in container when the analyte capture element is separated with device, this container can comprise suspension medium, lysis agent (for example, acid, alkali, washing composition, enzyme, proteolytic enzyme, N,O-Diacetylmuramidase, lysostaphin), analyte specific probe, analyte Auele Specific Primer within it and/or for amplifying or enzyme and the reagent of mark polynucleotide.
In certain embodiments, the method also can comprise enriching step.Enriching step can comprise provides substratum to be conducive to target microorganism and the growth that comprises inclusion (latent effervescent body) in the effervescence combination of selecting reagent, as be filed in the U.S. Patent application No.61/428 on December 31st, 2010, described in 856, it is incorporated herein by reference in full.
Embodiment
Embodiment 1 is a kind of device for the treatment of sample, and it comprises:
The sample receiving element;
The filtrate receiving element; With
The analyte capture element;
Wherein the sample receiving element comprises:
The first hollow body, the first Room that it has the first end, the second end and extends to the second end from the first end; With
Filtering element, it is arranged in the first Room between the first end and the second end;
Wherein the first end comprises the first opening that is configured to hold sample;
Wherein the second end comprises the second opening;
Wherein the filtrate receiving element comprises the second hollow body, and this second hollow body has the 3rd end, the 4th end and from the 3rd end, extends to the second Room of the 4th end; And
Wherein the 3rd end comprises and is configured to hold the 3rd opening that sample holds the second end of member;
Wherein the 4th end comprises the 4th opening;
Wherein the analyte capture element removably is connected to the filtrate receiving element;
Wherein when the sample receiving element is connected to the filtrate receiving element, device is formed with and is beneficial to flow and crosses the ，Gai fluid channel, fluid channel of the first Room, filtering element and the second Room and be conducive to the contact between fluid sample and analyte capture element;
Wherein the second end is formed and is proportional at least a portion that is fitted in the second Room is interior and vertically move at least a portion of passing the second Room.
Embodiment 2 is the device of embodiment 1, and wherein the analyte capture element further is arranged in the second Room.
Embodiment 3 is any one device in previous embodiment, also comprises the detachable inner sleeve with the 5th end and the 6th end, and the 5th end has the 5th opening, and the 6th end has the 6th opening, and wherein said sleeve pipe is arranged in the second Room.
Embodiment 4 is any one device in previous embodiment, also comprises porous supporting mass or foraminous shield.
Embodiment 5 is the device of embodiment 4, during wherein at least a portion of at least a portion of porous supporting mass or foraminous shield is arranged at the second hollow body between analyte capture element and the 4th opening.
Embodiment 6 is the device of embodiment 4 or embodiment 5, and wherein the analyte capture element is connected to porous supporting mass or foraminous shield.
Embodiment 7 is any one device in previous embodiment, and wherein filtering element further comprises a plurality of layers.
Embodiment 8 is any one device in embodiment 1 to 7, and wherein the second end is suitable for inserting in the second Room and moves through the point that the second hollow body arrives its contact analysis thing capture element, porous supporting mass or foraminous shield.
Embodiment 9 is a kind of device for the treatment of a plurality of samples, and it comprises:
The sample receiving element;
The filtrate receiving element; With
A plurality of analyte capture element;
Wherein the sample receiving element comprises:
The first main body, it has the first Room separated on the first end, the second end and a plurality of space, and each first Room extends to the second end from the first end;
Wherein the first end comprises a plurality of the first openings, and at least one first opening is configured to hold sample;
Wherein the second end comprises a plurality of outlets, and each outlet has the second opening;
Wherein the first main body forms a plurality of fluid channels, and each fluid channel extends to the second opening and passes the first Room therebetween from the first opening; With
A plurality of filtering elements, each filtering element are arranged in these a plurality of first Room, between the first and second openings;
Wherein the filtrate receiving element comprises:
The second main body, it has the second Room separated on the 3rd end, the 4th end and a plurality of space, and each second Room extends to the 4th end from the 3rd end, and each second Room comprises:
Be positioned at the 3rd opening of the 3rd end, the 3rd opening is configured to hold in these a plurality of outlets;
Be positioned at the 4th opening of the 4th end;
Wherein each in these a plurality of analyte capture element is connected to the filtrate receiving element;
Wherein when the sample receiving element is connected to the filtrate receiving element, device forms a plurality of fluid channels, each fluid channel is conducive to make flow to cross in in these a plurality of first Room, these a plurality of filtering elements and these a plurality of second Room, and is conducive to make these a plurality of analyte capture element of fluid contact at least one;
Wherein each in these a plurality of outlets is formed and is proportional at least a portion that is fitted in the second Room is interior and vertically move at least a portion of passing the second Room.
Embodiment 10 is the device of embodiment 9, and wherein at least one of this a plurality of analyte capture element also is arranged at least one of these a plurality of the second Room.
Embodiment 11 is the device of embodiment 9 or embodiment 10, at least one detachable inner sleeve with the 5th end and the 6th end, the 5th end has the 5th opening, and the 6th end has the 6th opening, and wherein said sleeve pipe is arranged at least one of these a plurality of the second Room.
Embodiment 12 is any one device in embodiment 9 to 11, at least one porous supporting mass or at least one foraminous shield.
Embodiment 13 is the device of embodiment 12, and at least a portion of wherein said at least one porous supporting mass or at least one foraminous shield is arranged at least one second Room between analyte capture element and the 4th end.
Embodiment 14 is any one device in embodiment 12 to 13, and wherein the analyte capture element is connected to the porous supporting mass.
Embodiment 15 is any one device in embodiment 9 to 14, and wherein said at least one filtering element further comprises a plurality of layers.
Embodiment 16 is any one device in embodiment 9 to 15, and wherein each in these a plurality of outlets is suitable for inserting in these a plurality of second Room and moves through the point that the second Room arrives its contact analysis thing capture element, porous supporting mass or foraminous shield.
Embodiment 17 is any one device in embodiment 1 to 16, and wherein the filtrate receiving element is configured to be connected to negative pressure source.
Embodiment 18 is any one device in embodiment 1 to 17, wherein at least one in sample receiving element or filtrate receiving element also comprises setting element, when the sample receiving element was connected to the filtrate receiving element, this setting element controllably kept the position of sample receiving element with respect to the filtrate receiving element.
Embodiment 19 is a kind of method that whether has analyte in sample that detects, and it comprises:
Any one device in liquid sample and embodiment 1 to 8 is provided;
Make liquid sample flow through filtering element;
Make filtrate contact analysis thing capture element;
The analyte capture element is separated with device; With
Whether detect analyte exists.
Embodiment 20 is the method for embodiment 19, also comprises device is attached to negative pressure source, wherein makes liquid sample flow through filtering element and comprises that further by negative pressure, pulling sample to make it pass filtering element filters rear sample to generate.
Embodiment 21 is the method for embodiment 20, wherein by negative pressure, pulls sample to make it pass filtering element and comprises that further by negative pressure, making to filter rear sample contacts with the analyte capture element.
Embodiment 22 is any one method in embodiment 19 to 21, the analyte capture element is separated with device further comprise with the second end to carry out the separate analytes capture element.
Embodiment 23 is the method for embodiment 22, wherein uses the second end to comprise that further promotion the second end passes the second Room with the separate analytes capture element.
Embodiment 24 is any one method in embodiment 19 to 23, after also being included in the separate analytes capture element, by lysis agent Treatment Analysis thing capture element.
Embodiment 25 is a kind of method that whether has analyte in a plurality of samples that detects, and it comprises:
Any one device in plurality of liquid sample and embodiment 9 to 18 is provided;
Make at least two kinds of liquid samples flow through in these a plurality of filtering elements at least two to generate at least two kinds of filtrates;
Make at least two analyte capture element of described at least two kinds of filtrates contact;
Described at least two analyte capture element are separated with device; With
Whether detect analyte exists.
Embodiment 26 is the method for embodiment 25, also comprise device is attached to negative pressure source, wherein make the plurality of liquid sample flow cross at least two filtering elements and further comprise by negative pressure and pull liquid sample to make it pass at least two filtering elements to produce sample after at least two kinds of filtrations.
Embodiment 27 is the method for embodiment 26, wherein by negative pressure, pulls a plurality of samples to make it pass at least two filtering elements and comprises that further by negative pressure, making to filter rear sample contacts with at least two analyte capture element.
Embodiment 28 is any one method in embodiment 25 to 27, at least two analyte capture element is separated with device further comprise with at least two outlets at least two analyte capture element are separated with device.
Embodiment 29 is the method for embodiment 28, wherein uses at least two outlets to comprise that further at least two outlets of promotion make it pass at least two the second Room so that at least two analyte capture element are separated with device.
Embodiment 30 is any one method in embodiment 25 to 29, after also being included at least two analyte capture element of separation, processes this at least two analyte capture element with the lysis agent.
Under the premise without departing from the spirit and scope of the present invention, can carry out various modifications.These and other embodiment all within the scope of the appended claims.
Claims (30)
1. device for the treatment of sample, described device comprises:
The sample receiving element;
The filtrate receiving element; With
The analyte capture element;
Wherein said sample receiving element comprises:
The first hollow body, described the first hollow body have the first end, the second end and from described the first end, extend to the first Room of described the second end; With
Filtering element, described filtering element are arranged in described the first Room between described the first end and the second end;
Wherein said the first end comprises the first opening that is configured to hold sample;
Wherein said the second end comprises the second opening;
Wherein said filtrate receiving element comprises the second hollow body, and described the second hollow body has the 3rd end, the 4th end and from described the 3rd end, extends to the second Room of described the 4th end; And
Wherein said the 3rd end comprises and is configured to hold the 3rd opening that described sample holds described second end of member;
Wherein said the 4th end comprises the 4th opening;
Wherein said analyte capture element is connected to described filtrate receiving element in the mode that can dismantle;
Wherein when described sample receiving element is connected to described filtrate receiving element, described device is formed with and is beneficial to the fluid channel that flow is crossed described the first Room, described filtering element and described the second Room, and described fluid channel is conducive to contacting between fluid sample and described analyte capture element;
Wherein said the second end is formed and is proportional at least a portion that is fitted in described the second Room is interior and vertically move at least a portion of passing described the second Room.
2. device according to claim 1, wherein said analyte capture element further is arranged in described the second Room.
3. according to device in any one of the preceding claims wherein, also comprise the inner sleeve that can remove with the 5th end and the 6th end, described the 5th end has the 5th opening, and described the 6th end has the 6th opening, and wherein said inner sleeve is arranged in described the second Room.
4. according to device in any one of the preceding claims wherein, also comprise porous supporting mass or foraminous shield.
5. device according to claim 4, at least a portion of wherein said porous supporting mass or at least a portion of described foraminous shield arrange described the second hollow body between described analyte capture element and described the 4th opening in.
6. according to claim 4 or device claimed in claim 5, wherein said analyte capture element is connected to described porous supporting mass or foraminous shield.
7. according to device in any one of the preceding claims wherein, wherein said filtering element further comprises a plurality of layers.
8. according to device in any one of the preceding claims wherein, wherein said the second end is suitable for being inserted in described the second Room and moves through the point that described the second hollow body arrives contact described analyte capture element, porous supporting mass or foraminous shield.
9. device for the treatment of a plurality of samples, described device comprises:
The sample receiving element;
The filtrate receiving element; With
A plurality of analyte capture element;
Wherein said sample receiving element comprises:
The first main body, described the first main body has the first Room separated on the first end, the second end and a plurality of space, and each first Room extends to described the second end from described the first end;
Wherein said the first end comprises a plurality of the first openings, and at least one first opening is configured to hold sample;
Wherein said the second end comprises a plurality of outlets, and each outlet has the second opening;
Wherein said the first main body forms a plurality of fluid channels, and each fluid channel extends to the second opening and passes the first Room therebetween from the first opening; With
A plurality of filtering elements, each filtering element are arranged in described a plurality of the first Room, between described the first opening and the second opening;
Wherein said filtrate receiving element comprises:
The second main body, described the second main body has the second Room separated on the 3rd end, the 4th end and a plurality of space, and each second Room extends to described the 4th end from described the 3rd end, and each second Room comprises:
Be positioned at the 3rd opening of described the 3rd end, described the 3rd opening is configured to hold in described a plurality of outlet;
Be positioned at the 4th opening of described the 4th end;
Each in wherein said a plurality of analyte capture element is connected to described filtrate receiving element;
Wherein when described sample receiving element is connected to described filtrate receiving element, described device forms a plurality of fluid channels, each fluid channel is conducive to make flow to cross in in described a plurality of the first Room, described a plurality of filtering elements and described a plurality of the second Room, and is conducive to make at least one in the described a plurality of analyte capture element of fluid contact;
Each in wherein said a plurality of outlet is formed and is proportional at least a portion that is fitted in described the second Room is interior and vertically move at least a portion of passing described the second Room.
10. device according to claim 9, at least one in wherein said a plurality of analyte capture element further is arranged at least one of described a plurality of the second Room.
11. according to claim 9 or device claimed in claim 10, also comprise at least one inner sleeve that can remove with the 5th end and the 6th end, described the 5th end has the 5th opening, described the 6th end has the 6th opening, and wherein said inner sleeve is arranged at least one of described a plurality of the second Room.
12., according to the described device of any one in claim 9 to 11, also comprise at least one porous supporting mass or at least one foraminous shield.
13. device according to claim 12, at least a portion wherein said at least one porous supporting mass or described at least one foraminous shield are arranged at least one second Room between described analyte capture element and described the 4th end in.
14. according to claim 12 or the described device of claim 13, wherein said analyte capture element is connected to described porous supporting mass or foraminous shield.
15. according to the described device of any one in claim 9 to 14, wherein said at least one filtering element further comprises a plurality of layers.
16. according to the described device of any one in claim 9 to 15, each in wherein said a plurality of outlets be suitable for inserting described a plurality of the second Room in one in and move through the point that this second Room arrives contact described analyte capture element, porous supporting mass or foraminous shield.
17. according to the described device of any one in claim 1 to 16, wherein said the 4th end is configured to be connected to negative pressure source.
18. according to the described device of any one in claim 1 to 17, at least one in wherein said sample receiving element or filtrate receiving element also comprises setting element, when described sample receiving element was connected to described filtrate receiving element, described setting element kept the position of described sample receiving element with respect to described filtrate receiving element in the mode that can control.
19. whether one kind for detection of existing the method for analyte in sample, described method comprises:
Liquid sample and device as described as any one in claim 1 to 8 are provided;
Make described liquid sample flow through described filtering element;
Make the described analyte capture element of filtrate contact;
Described analyte capture element is separated with described device; With
Whether detect described analyte exists.
20. method according to claim 19, also comprise described device is attached to negative pressure source, wherein make described liquid sample flow through described filtering element and comprise that further by negative pressure, pulling described sample to make it pass described filtering element filters rear sample to generate.
21. method according to claim 20, wherein with negative pressure pull described sample make its pass described filtering element further comprise by described negative pressure, make described filtration after sample with described analyte capture element, contact.
22., according to claim 19 to the described method of any one in 21, described analyte capture element is separated with described device further comprise with described the second end described analyte capture element is separated with described device.
23. method according to claim 22, wherein used described the second end to comprise that further described the second end of promotion passes described the second Room so that described analyte capture element is separated with described device.
24., according to claim 19 to the described method of any one in 23, after also being included in and separating described analyte capture element, process described analyte capture element with the lysis agent.
25. whether one kind for detection of existing the method for analyte in a plurality of samples, described method comprises:
A plurality of liquid samples and device as described as any one in claim 9 to 18 are provided;
Make at least two liquid samples flow through at least two in described a plurality of filtering element, to generate at least two filtrates;
Make at least two analyte capture element of described at least two filtrates contact;
Described at least two analyte capture element are separated with described device; With
Whether detect described analyte exists.
26. method according to claim 25, also comprise described device is attached to negative pressure source, wherein make a plurality of liquid samples flow through described at least two filtering elements and further comprise by negative pressure and pull described liquid sample to make it pass described at least two filtering elements, to generate sample after at least two filtrations.
27. method according to claim 26, wherein pull a plurality of samples to make it pass described at least two filtering elements by negative pressure and comprise that further by described negative pressure, making to filter rear sample contacts at least with described two analyte capture element.
28., according to the described method of any one in claim 25 to 27, described at least two analyte capture element are separated with described device further comprise with at least two outlets described at least two analyte capture element are separated with described device.
29. method according to claim 28, wherein used at least two outlets to comprise that further described at least two outlets of promotion make it pass described at least two the second Room so that described at least two analyte capture element are separated with described device.
30., according to the described method of any one in claim 25 to 29, after also being included in described at least two the analyte capture element of separation, process described at least two analyte capture element with the lysis agent.
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| US61/451,096 | 2011-03-09 | ||
| PCT/US2012/027699 WO2012122088A1 (en) | 2011-03-09 | 2012-03-05 | Apparatus and method for processing a sample |
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| CN103415617A true CN103415617A (en) | 2013-11-27 |
| CN103415617B CN103415617B (en) | 2016-03-02 |
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| US (2) | US9255864B2 (en) |
| EP (1) | EP2683820B1 (en) |
| JP (1) | JP5959542B2 (en) |
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| BR (1) | BR112013022735A2 (en) |
| MX (1) | MX338703B (en) |
| WO (1) | WO2012122088A1 (en) |
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Also Published As
| Publication number | Publication date |
|---|---|
| US9255864B2 (en) | 2016-02-09 |
| BR112013022735A2 (en) | 2016-12-06 |
| JP2014507670A (en) | 2014-03-27 |
| MX338703B (en) | 2016-04-28 |
| WO2012122088A1 (en) | 2012-09-13 |
| MX2013010123A (en) | 2013-10-07 |
| EP2683820B1 (en) | 2019-05-22 |
| CN103415617B (en) | 2016-03-02 |
| US20130344478A1 (en) | 2013-12-26 |
| US20160153874A1 (en) | 2016-06-02 |
| JP5959542B2 (en) | 2016-08-02 |
| US9784653B2 (en) | 2017-10-10 |
| EP2683820A1 (en) | 2014-01-15 |
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